Citrin deficiency is a rare autosomal recessive metabolic disorder caused by pathogenic variants in the SLC25A13 gene. Pregnancy in affected women is uncommon and presents unique challenges because conventional obstetric management may conflict with metabolic requirements. The coexistence of gestational diabetes mellitus (GDM) introduces additional complexity. A 25-year-old, gravida 2 para 0+1 woman with genetically confirmed citrin deficiency (homozygous SLC25A13 c.1763G>A mutation) was managed jointly by obstetric and inherited metabolic disease (IMD) teams. Her pregnancy was complicated by severe nausea and vomiting during the first trimester and subsequent GDM diagnosed using capillary glucose monitoring rather than an oral glucose tolerance test. Representative fasting glucose values were 6.3-6.8 mmol/L, with postprandial values up to 10.7 mmol/L. Specialist dietary modification and insulin therapy were instituted following multidisciplinary review. A personalised metabolic plan emphasised avoidance of prolonged fasting, restriction of excessive carbohydrate intake, maintenance of adequate energy intake, and avoidance of routine glucose-containing intravenous fluids. At 38+5 weeks' gestation, she underwent emergency caesarean section for failure to progress in labour under spinal anaesthesia. A healthy infant weighing 3074 g was delivered with Apgar scores of 9, 10 and 10 at 1, 5 and 10 minutes, respectively. Postoperative pain management was challenging because the specialist metabolic plan advised caution with paracetamol. Following inadequate analgesia with ibuprofen and dihydrocodeine, paracetamol was cautiously introduced at reduced doses and subsequently increased to 500 mg four times daily, with additional opioid analgesia as required. Daily plasma ammonia and liver function monitoring was undertaken during the five-day postoperative admission; ammonia values remained within the laboratory reference range, with no hyperammonaemia (range <10-32 µmol/L) or significant hepatic biochemical deterioration. This case highlights the complexity of managing pregnancy in women with citrin deficiency, particularly when complicated by GDM. It also demonstrates a practical approach to postoperative analgesia following caesarean delivery using cautious dose escalation and biochemical surveillance.

Percutaneous nephrolithotomy (PCNL) is the gold standard for large renal calculi, yet postoperative pain from tract dilation, capsule injury, and inflammation often delays recovery, prolongs hospital stays, and reduces patient satisfaction. Amid the opioid crisis, reliance on opioids for pain control raises concerns over adverse effects like respiratory depression, nausea, and dependence. This has spurred interest in opioid-sparing multimodal strategies, with recent studies suggesting feasibility of opioid-free discharge and comparable relief from NSAIDs with fewer side effects. However, robust comparative evidence remains scarce. This systematic review and network meta-analysis (NMA) evaluates and ranks postoperative analgesic strategies in PCNL, aiming to highlight approaches that may reduce opioid use while improving clinical outcomes in endourology. We searched PubMed, Embase, Web of Science, and Cochrane Library up to March 11, 2025 for RCTs assessing VAS pain in adults undergoing PCNL. Interventions grouped: local anesthesia/nerve blocks, intravenous analgesics, local instillation, intrathecal anesthesia, aromatherapy. Bayesian NMA used ADDIS v1.16.8/R v4.0.5, with MCMC simulations, node-splitting for consistency, SMAA for benefit-risk of VAS (<24h, ≥24h) and complications. 45 RCTs (2,626 patients) formed consistent network without significant inconsistency/heterogeneity. Levobupivacaine outperformed bupivacaine/ropivacaine in VAS reduction (<24h, ≥24h) via erector spinae plane block/local infiltration. Non-opioid analgesics (NSAIDs/paracetamol) showed superior efficacy; opioids excelled short-term but not long-term. IV paracetamol plus LI-levobupivacaine ranked highest in the multicriteria analysis, although the benefit-risk ranking should be interpreted cautiously because the safety component was based on sparse and imprecise data. Limitations: RCT protocol variability (e.g., pain assessment), moderate bias in 21 studies, limited data for high-risk subgroups (e.g., renal impairment, obesity). Comparative safety could not be established because complication data were sparse and estimates were highly imprecise. This NMA supports levobupivacaine and NSAID-based IV analgesics for PCNL pain management, positioning IV-Paracetamol+LI-Levobupivacaine as a leading opioid-sparing multimodal option to address complex pain profiles. These findings encourage safer practices amid opioid concerns, potentially accelerating recovery, shortening stays, and enhancing endourology patient outcomes.Trial registration: PROSPERO CRD42024600872.

Alcohol-induced dose dumping is a significant concern for modified-release oral dosage forms, as it can compromise the intended release behaviour. For enteric-coated formulations, alcohol exposure may lead to loss of enteric functionality and unintended premature drug release in the stomach. Although previous studies have mainly assessed the loss of enteric performance in delayed-release dosage forms, the mechanisms underlying alcohol-induced changes remain poorly understood. In this study, the behaviour of isolated hydroxypropyl methylcellulose phthalate (HPMC-P) films was investigated in aqueous ethanolic media containing 0-40% v/v ethanol. Film permeability was evaluated using paracetamol, nicotinamide and tritiated water as model permeants. No significant change in permeability was observed at ethanol concentrations up to 20% v/v. However, exposure to 40% v/v ethanol significantly increased permeability. Under these conditions, permeability differences between paracetamol (4.4 ± 0.6 E-05 cm/s) and nicotinamide (2.4 ± 0.3 E-05 cm/s) were observed and were initially attributed to differences in drug solubility in hydroalcoholic medium. However, studies with tritiated water eliminated solubility-related effects and provided direct evidence of ethanol-induced changes in film permeability. Microscopic imaging revealed ethanol concentration dependent pore formation within the films. Mass loss study showed negligible film erosion even at 40% v/v ethanol, despite the substantial increase in permeability. These findings demonstrate that increased film permeability originates primarily from ethanol-induced microstructural changes rather than polymer erosion. Overall, this work provides mechanistic insights into the effects of ethanol exposure on HPMC-P films and improves understanding of alcohol-induced alterations in enteric-coated formulations.

IntroductionMetastasis occurs in almost 50% of patients with uveal melanoma. In patients who are HLA-A*02:01 positive, first line treatment is the Immune mobilizing monoclonal T cell receptor Against Cancer (ImmTAC), tebentafusp, which increases overall survival significantly at one year compared to single-agent immunotherapy or chemotherapy. Hypersensitivity reactions (HSR) to cancer therapeutics are well established. When these therapies offer significant benefits over alternatives, drug desensitization protocols are utilized to improve clinical outcomes in those with suspected IgE-mediated HSRs.Case reportWe present a case of an individual with metastatic uveal melanoma who suffered an anaphylactic HSR to tebentafusp. Given the lack of available ImmTAC therapeutic desensitization protocols, this report's purpose was to create a tebentafusp desensitization protocol based on accepted desensitization protocols for other chemotherapeutic drugs.Management and outcomeThe desensitization procedure consisted of pretreatment with cetirizine, famotidine, diphenhydramine, methylprednisolone, and acetaminophen prior to infusion. Infusions were each given as two diluted infusions limited to 100 mL of reconstitution volume, with cumulative quantities equivalent to standard treatment regimen dosages. Drug was given over no longer than four hours per manufacturer's recommendations. A total of three cycles of three weekly infusions were completed. The patient had no anaphylaxis recurrence. Tebentafusp treatment was withheld after the third cycle due to disease progression.DiscussionFor patients with HLA-A*02:01 positive metastatic uveal melanoma with suspected IgE-mediated HSR to tebentafusp, desensitization can be completed safely. Given the patient's disease progression within two months of treatment, it is unknown whether desensitization impacts the drug's clinical benefit.

Oral delivery of water-repelling drugs for acute liver failure (ALF) often runs into problems like poor solubility, instability, and low absorption. In this work, we found that extracellular vesicles derived from honey (HEVs) can serve as a natural nanocarrier that works orally and targets the liver on its own. After isolating and characterizing these vesicles, we saw they are membrane-bound nanoparticles roughly 160 nm in size with a surface charge around -32 mV, and they contain proteins and RNAs. Oral HEVs mainly ended up in the liver and showed some anti-inflammatory activity without any drug loaded. To get better therapeutic effects, we loaded curcumin (Cur), a hydrophobic anti-inflammatory compound, into HEVs to make Cur@HEVs. These loaded vesicles greatly improved how well curcumin is absorbed and released in a sustained manner. In acetaminophen (APAP) caused ALF mice, oral Cur@HEVs improved liver function and survival much more than plain curcumin or empty HEVs did. Specifically, Cur@HEVs simultaneously put the brakes on pyroptosis (via the NLRP3/GSDMD/caspase-1 route) and necroptosis (through the RIPK1/RIPK3/MLKL pathway), which in turn cut down the release of inflammatory cytokines and kept liver cells from dying. Overall, HEVs come across as a safe, food-based nanocarrier that can be taken orally, and Cur@HEVs offer a bioactive platform for dually targeting inflammatory cell death in ALF. Our findings suggest that dietary extracellular vesicles warrant further investigation as potential therapeutic biomaterials, though additional translational studies are needed.

The occurrence of paracetamol in water motivates the development of treatment processes that combine contaminant removal with reduced dependence on grid electricity. Iron-electrode electrocoagulation was optimized using a regulated direct-current power supply, a face-centered central composite design, and response surface methodology. The initial paracetamol concentration (0.1-0.3 mg·mL[-1]), reaction time (10-30 min), current density (0.95-6.67 A·m[-2]), and initial pH (3.0-10.0) were evaluated. The quadratic model was statistically significant (F = 3.072; p = 0.0293; R[2] = 0.7818; adjusted R[2] = 0.5273) and revealed significant interactions between current density and pH, concentration and current density, concentration and pH, and reaction time and pH. The highest experimental removal was 90.7%, obtained at 0.2 mg·mL[-1], 30 min, 3.81 A·m[-2], and pH 6.5, with a residual concentration of 18.6 mg·L[-1]. Near-zero ζ-potential values and floc growth up to approximately 44 μm were consistent with charge neutralization and sweep coagulation, although they did not establish a unique removal mechanism. The selected condition was subsequently operated using a configuration comprising a photovoltaic module, an MPPT controller, and a battery; photovoltaic supply was not a factor in the experimental design. At the maximum-removal condition, both configurations exhibited the same reactor energy consumption (0.018315 kWh·m[-3]) and theoretical iron dissolution (0.001737 kg·m[-3]). However, when a marginal purchase price of zero was assigned to photovoltaic electricity, the solar configuration was more cost-efficient than the conventional configuration: the partial variable cost decreased from BRL 0.013482·m[-3]to BRL 0.000495·m[-3], corresponding to a 96.33% reduction. This comparison excludes photovoltaic system capital investment, battery replacement, maintenance, sludge management, labor, and life-cycle costs. The results identify a favorable operating region at the batch scale, although the resulting residual concentration does not demonstrate compliance with a discharge criterion.